Sputum culture conversion in new TB regimens

Abstract Background Pyrazinamide (PZA) resistance in multidrug-resistant tuberculosis (MDR-TB) is common; yet, it is not clear how it affects interim and treatment outcomes. Although rarely performed, phenotypic drug susceptibility testing (pDST) is used to define PZA resistance, but genotypic DST (gDST) and minimum inhibitory concentration (MIC) could be beneficial. We aimed to assess the impact of PZA gDST and MIC on time to sputum culture conversion (SCC) and treatment outcome in patients with MDR-TB. Methods Clinical, microbiological, and treatment data were collected in this cohort study for all patients diagnosed with MDR-TB in Sweden from 1992–2014. MIC, pDST, and whole-genome sequencing of the pncA, rpsA, and panD genes were used to define PZA resistance. A Cox regression model was used for statistical analyses. Results Of 157 patients with MDR-TB, 56.1% (n = 88) had PZA-resistant strains and 49.7% (n = 78) were treated with PZA. In crude and adjusted analysis (hazard ratio [HR], 0.49; 95% conficence interval [CI], .29-.82; P = .007), PZA gDST resistance was associated with a 29-day longer time to SCC. A 2-fold decrease in dilutions of PZA MIC for PZA-susceptible strains showed no association with SCC in crude or adjusted analyses (HR, 0.98; 95% CI, .73–1.31; P = .89). MIC and gDST for PZA were not associated with treatment outcome. Conclusions In patients with MDR-TB, gDST PZA resistance was associated with a longer time to SCC. Rapid PZA gDST is important to identify patients who may benefit from PZA treatment.

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Culture Conversion at 6 Months in Patients Receiving Delamanid-containing Regimens for the Treatment of Multidrug-resistant Tuberculosis

Clinical Infectious Diseases ◽

10.1093/cid/ciz1084 ◽

2019 ◽

Vol 71 (2) ◽

pp. 415-418 ◽

Cited By ~ 1

Author(s):

Kwonjune J Seung ◽

Palwasha Khan ◽

Molly F Franke ◽

Saman Ahmed ◽

Stalbek Aiylchiev ◽

...

Keyword(s):

Clinical Trials ◽

Observational Study ◽

Multidrug Resistant ◽

Sputum Culture ◽

Drug Markets ◽

Sputum Culture Conversion ◽

Resistant Tuberculosis ◽

Multidrug Resistant Tuberculosis ◽

Resistant Strains ◽

Culture Conversion

Abstract Delamanid should be effective against highly resistant strains of Mycobacteriumtuberculosis, but uptake has been slow globally. In the endTB (expand new drug markets for TB) Observational Study, which enrolled a large, heterogeneous cohorts of patients receiving delamanid as part of a multidrug regimen, 80% of participants experienced sputum culture conversion within 6 months. Clinical Trials Registration. NCT02754765.

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Isoniazid and Rifampin-Resistance Mutations Associated With Resistance to Second-Line Drugs and With Sputum Culture Conversion

The Journal of Infectious Diseases ◽

10.1093/infdis/jiaa042 ◽

2020 ◽

Vol 221 (12) ◽

pp. 2072-2082 ◽

Cited By ~ 2

Author(s):

Eleanor S Click ◽

Ekaterina V Kurbatova ◽

Heather Alexander ◽

Tracy L Dalton ◽

Michael P Chen ◽

...

Keyword(s):

Cox Regression ◽

Acquired Resistance ◽

Sputum Culture ◽

Fluoroquinolone Resistance ◽

Cross Resistance ◽

Bivariate Analysis ◽

Molecular Testing ◽

Resistance Mutations ◽

Sputum Culture Conversion ◽

Culture Conversion

Abstract Background Mutations in the genes inhA, katG, and rpoB confer resistance to anti-tuberculosis (TB) drugs isoniazid and rifampin. We questioned whether specific mutations in these genes were associated with different clinical and microbiological characteristics. Methods In a multicountry prospective cohort study of multidrug-resistant TB, we identified inhA, katG, and rpoB mutations in sputum isolates using the Hain MTBDRplus line probe assay. For specific mutations, we performed bivariate analysis to determine relative risk of baseline or acquired resistance to other TB drugs. We compared time to sputum culture conversion (TSCC) using Kaplan-Meier curves and stratified Cox regression. Results In total, 447 participants enrolled from January 2005 to December 2008 from 7 countries were included. Relative to rpoB S531L, isolates with rpoB D516V had less cross-resistance to rifabutin, increased baseline resistance to other drugs, and increased acquired fluoroquinolone resistance. Relative to mutation of katG only, mutation of inhA promoter and katG was associated with baseline extensively drug resistant (XDR) TB, increased acquired fluoroquinolone resistance, and slower TSCC (125.5 vs 89.0 days). Conclusions Specific mutations in inhA and katG are associated with differences in resistance to other drugs and TSCC. Molecular testing may make it possible to tailor treatment and assess additional drug resistance risk according to specific mutation profile.

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Comparison of Sputum-Culture Conversion forMycobacterium bovisandM. tuberculosis

Emerging Infectious Diseases ◽

10.3201/eid2303.161916 ◽

2017 ◽

Vol 23 (3) ◽

pp. 456-462 ◽

Cited By ~ 2

Author(s):

Colleen Scott ◽

Joseph S. Cavanaugh ◽

Benjamin J. Silk ◽

Julia Ershova ◽

Gerald H. Mazurek ◽

...

Keyword(s):

Sputum Culture ◽

Sputum Culture Conversion ◽

Culture Conversion

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Predictors of sputum culture conversion among patients treated for multidrug-resistant tuberculosis

The International Journal of Tuberculosis and Lung Disease ◽

10.5588/ijtld.11.0811 ◽

2012 ◽

Vol 16 (10) ◽

pp. 1335-1343 ◽

Cited By ~ 38

Author(s):

E. V. Kurbatova ◽

V. M. Gammino ◽

J. Bayona ◽

M. C. Becerra ◽

M. Danilovitz ◽

...

Keyword(s):

Multidrug Resistant ◽

Sputum Culture ◽

Sputum Culture Conversion ◽

Resistant Tuberculosis ◽

Multidrug Resistant Tuberculosis ◽

Culture Conversion

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Impact of smoking on sputum culture conversion and pulmonary tuberculosis treatment outcomes in Brazil: a retrospective cohort study

Jornal Brasileiro de Pneumologia ◽

10.1590/s1806-37562017000000161 ◽

2018 ◽

Vol 44 (2) ◽

pp. 99-105 ◽

Cited By ~ 3

Author(s):

Michelle Cailleaux-Cezar ◽

Carla Loredo ◽

José Roberto Lapa e Silva ◽

Marcus Barreto Conde

Keyword(s):

Cohort Study ◽

Relative Risk ◽

Pulmonary Tuberculosis ◽

Treatment Outcomes ◽

Retrospective Cohort ◽

Sputum Culture ◽

Sputum Culture Conversion ◽

Poor Treatment ◽

Never Smokers ◽

Culture Conversion

ABSTRACT Objective: To evaluate the impact of smoking on pulmonary tuberculosis (PTB) treatment outcomes and the two-month conversion rates for Mycobacterium tuberculosis sputum cultures among patients with culture-confirmed PTB in an area with a moderate incidence of tuberculosis in Brazil. Methods: This was a retrospective cohort study of PTB patients diagnosed and treated at the Thoracic Diseases Institute of the Federal University of Rio de Janeiro between 2004 and 2012. Results: Of the 298 patients diagnosed with PTB during the study period, 174 were included in the outcome analysis: 97 (55.7%) were never-smokers, 31 (17.8%) were former smokers, and 46 (26.5%) were current smokers. Smoking was associated with a delay in sputum culture conversion at the end of the second month of TB treatment (relative risk = 3.58 &091;95% CI: 1.3-9.86&093;; p = 0.01), as well as with poor treatment outcomes (relative risk = 6.29 &091;95% CI: 1.57-25.21&093;; p = 0.009). The association between smoking and a positive culture in the second month of treatment was statistically significant among the current smokers (p = 0.027). Conclusions: In our sample, the probability of a delay in sputum culture conversion was higher in current smokers than in never-smokers, as was the probability of a poor treatment outcome.

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